Our principal effort is directed to understanding the mechanisms by which novel DNA rearrangements occur in vivo. We have concentrated on two major systems: bacterial viruses capable of integration and excision and herpes simplex virus (HSV). Phage lambda is used for both in vivo and in vitro recombination systems and for cloning DNA fragments of HSV. We are analysing the mechanism by which phage lambda integrates through genetic manipulation of the integrase enzyme as well as through isolation of phages with altered integration sites. We are using lambda-HSV recombinants to define and characterize regions of HSV DNA rearrangement. We are analyzing one HSV fragment that is very unstable when propagated in E. coli. Similarly, we are studying a cloned DNA fragment carrying an integrated MSV proviral genome (Moloney Sarcoma Virus - transformed mink cells) that is highly unstable in E. coli. Techniques to isolate, characterize and quantitate deletion formation in DNA fragments carried by phage lambda vectors have been established. A fine structure deletion map of the HSV Us region has been constructed using lambda-HSV hybrids.